title: Sensitive liquid chromatography/mass spectrometry methods for quantification of pomalidomide in mouse plasma and brain tissue.
abstract: Pomalidomide was recently approved by the United States Food and Drug Administration for the treatment of patients with relapsed or refractory multiple myeloma who have received at least two prior therapies. As pomalidomide is increasingly evaluated in other diseases and animal disease models, this paper presents development and validation of a sensitive liquid chromatography tandem mass spectrometry assay for quantification of pomalidomide in mouse plasma and brain tissue to fill a gap in published preclinical pharmacokinetic and analytical data with this agent. After acetonitrile protein precipitation, pomalidomide and internal standard, hesperitin, were separated with reverse phase chromatography on a C-18 column with a gradient mobile phase of water and acetonitrile with 0.1% fomic acid. Positive atmospheric pressure chemical ionization mass spectrometry with selected reaction monitoring mode was applied to achieve 0.3-3000nM (0.082-819.73ng/mL) linear range in mouse plasma and 0.6-6000pmol/g in brain tissue. The within- and between-batch accuracy and precision were less than 15% for both plasma and brain tissue. The method was applied to measure pomalidomide concentrations in plasma and brain tissue in a pilot mouse pharmacokinetic study with an intravenous dose of 0.5mg/kg. This assay can be applied for thorough characterization of pomalidomide pharmacokinetics and tissue distribution in mice.
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, United States.
authors.forename: Yao
authors.initials: Y
authors.lastname: Jiang
authors.forename: Jiang
authors.initials: J
authors.lastname: Wang
authors.forename: Darlene M
authors.initials: DM
authors.lastname: Rozewski
authors.forename: Shamalatha
authors.initials: S
authors.lastname: Kolli
authors.forename: Chia-Hsien
authors.initials: CH
authors.lastname: Wu
authors.forename: Ching-Shih
authors.initials: CS
authors.lastname: Chen
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Yang
authors.forename: Craig C
authors.initials: CC
authors.lastname: Hofmeister
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Johnson
authors.forename: Mitch A
authors.initials: MA
authors.lastname: Phelps
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects*; D002853:Chromatography, Liquid; D007155:Immunologic Factors / Q000097:blood / Q000493:pharmacokinetics; D016014:Linear Models; D051379:Mice; D011786:Quality Control; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D007155:Immunologic Factors; D013792:Thalidomide; C467566:pomalidomide
keywords: Brain; Liquid chromatography–mass spectrometry; Mouse; Pharmacokinetics; Pomalidomide